Objective:To explore the clinicopathological characteristics and the related influencing factors of efficacy and prognosis of elderly patients with malignant mesothelioma(MM)in Chinese population.Methods:We retrospectively analyzed the clinical data of 115 patients aged 65 years and above who were diagnosed with MM in Beijing Hospital, Peking University Cancer Hospital, and Cancer Hospital of Chinese Academy of Medical Sciences between November 2007 and July 2024, and the patients were grouped according to age(≥75 years in the older group and <75 years in the younger group), histological types and therapy regimens.Kaplan-Meier curve and Log-rank test were performed.Cox regression was used in prognostic analysis.Results:The positive expression rate of Calretinin in the Chinese elderly population with MM was consistent with previous reports, while the positive rates of Cytokeratin 5/6(CK5/6), WT-1, and D2-40 were much lower.The overall response ratio(ORR)for first-line treatment was 17.3%(9/52), and the disease control rate(DCR)was 92.3%(48/52).The ORR for second-line treatment was 7.7%(1/13)and the DCR was 76.9%(10/13).The ORR and DCR were higher in the first-line immunotherapy group than in the chemotherapy group, 50.0% vs.14.6%( P=0.134)and 100.0% vs.91.6%( P=1.000), respectively.The ORR in the second-line immunotherapy group was higher than that in the chemotherapy group, 25.0% vs.0, respectively, and the DCR were both 75.0% in two groups.The median progression free survival(mPFS)was 9.2 months and median overall survival(mOS)was 19.0 months for patients receiving first-line treatment, and the mPFS was 3.3 months and mOS was 11.0 months for second-line therapy.The first-line immunotherapy provided more shorter mPFS(1.6 months vs.9.2 months, P=0.081)and longer mOS(not reached vs.18.1 months, P=0.147)than the chemotherapy group.The younger group had prolonged mPFS(9.7 months vs.7.2 months, P=0.305)while shorter mOS(18.1 months vs.23.9 months, P=0.289)compared with the older group, and none of them reached statistical differences.Both mPFS and mOS were prolonged in the epithelioid subtype compared with the non-epithelioid subtypes, 10.4 months vs.1.6 months( P<0.001)and 20.3 months vs.4.6 months( P=0.803), respectively.Both mPFS(7.1 months vs.4.7 months, P=0.583)and mOS(18.3 months vs.6.3 months, P=0.134)were prolonged in the second-line chemotherapy group compared with the immunotherapy group.The Cox regression analysis showed that gender, Eastern Cooperative Oncology Group, Performance Status(ECOG PS)and positive CK5/6 were both the independent predictors for the first-line PFS.Histological type was an independent prognostic factor for the first-line OS. Conclusions:MM in the Chinese elderly population exhibits unique clinicopathologic characteristics.The immunotherapy improves ORR, DCR and prolongs mOS in first-line use, and improves ORR in second-line.First-line treatment improves mPFS in the younger group compared with the older group.Multivariate Cox regression demonstrates that gender, ECOG PS and CK5/6 expression are both predictors of efficacy, and histological type is an independent prognostic factor for survival of the Chinese elderly population with MM.

Objective:To investigate the efficacy and adverse effects of first-line immunotherapy combined with chemotherapy in elderly patients with small cell lung cancer(SCLC)in population of real world.Methods:A total of 148 elderly SCLC patients(age ≥65 years old)underwent pathological diagnosis were retrospectively analyzed from January 2013 to June 2023.103 patients received chemotherapy(chemotherapy group), and 45 patients received immunotherapy combined with chemotherapy(combination group). Patients were divided into senior group(≥75 years old)and younger group(<75 years old)by age.To compare the efficacy of different regimens in first-line treatment, the expression of programmed death-ligand 1(PD-L1)and tumor mutational burden(TMB)were evaluated.Response evaluation criteria in solid tumors(RECIST)version 1.1 was used to evaluate the efficacy, and common terminology criteria for adverse events(CTCAE)version 4.03 was used to evaluate immune-related adverse.Kaplan-meier and Log-rank test were performed.Cox regression was used in prognostic analysis.Results:The overall response rate(ORR)of the first-line combination group in elderly SCLC patients was 79.1%(34/43), which was higher than that of the chemotherapy group 63.2%(60/95), but the difference did not reach statistical significance( χ2=3.451, P=0.063). ORR was significantly higher in the combination group than in the chemotherapy group for patients in the ≥75-year-old group, 87.5%(7/8) vs.48.6%(17/35), respectively( χ2=4.001, P=0.045). The difference in median progression-free survival time(mPFS)in the combination group compared with the chemotherapy group was not statistically significant in the overall patients(5.43 months vs.6.07 months, P=0.660). The combination group prolonged patients' median overall survival time(mOS)compared with the chemotherapy group, but the difference did not reach statistical significance(13.63 months vs.11.97 months, P=0.205). In patients ≥75 years old, mPFS was lower in the combination group than in the chemotherapy group(2.97 months vs.6.47 months), but mOS was prolonged compared with that in the chemotherapy group(13.50 months vs.11.40 months), and none of the differences reached statistical significance(both P>0.05). The differences in mPFS and mOS between the combination group and the chemotherapy group were not statistically significant in patients <75 years old(both P>0.05). In elderly patients with severe comorbidities, mPFS and mOS were lower in the combination group than in the chemotherapy group(5.40 months vs.7.30 months and 10.70 months vs.12.27 months, both P>0.05). In patients without severe comorbidities, the difference in mPFS between the combination group and the chemotherapy group was not statistically significant( P>0.05), but the mOS was significantly longer in the combination group(20.57 months vs.11.57 months, P=0.054). Elderly SCLC patients had a positive PD-L1 tumor cell positive proportion score(TPS)rate(≥1%)of 23.5%(4/17)and a high TMB(≥9 mut/Mb)expression rate of 69.0%(11/16). The overall incidence of immune-related adverse reactions was 71.0%(32/45), grade 3 or higher 33.3%(15/45), and the most common grade 3 adverse reactions were rash, immune-related pneumonia and malaise. Conclusions:First-line immune-combination chemotherapy improves ORR and mOS over chemotherapy in elderly SCLC patients; mOS benefit of immune-combination chemotherapy is more pronounced in patients ≥75 years of age without severe comorbidities, low PD-L1 positivity and high TMB expression are present in elderly SCLC patients, and immune-related adverse effects are generally manageable in elderly patients.

BACKGROUND: Immune checkpoint inhibitors (ICIs) improved survival of partial patients with lung squamous cell carcinoma (LUSC). However, it was still insufficient of data in older patients. This study aimed to investigate the efficacy and toxicity of immunotherapy in patients with LUSC in Chinese population of real world. METHODS: A total of 185 LUSC patients underwent pathological diagnosis were involved from January 2018 to January 2022. Patients were divided into elderly group (age ≥70 years) and younger group (age <70 years). The efficacy of mono-immunotherapy or combined with chemotherapy to chemotherapy in first-line treatment was compared. The expression of programmed cell death ligand 1 (PD-L1) and tumor mutational burden (TMB) were evaluated. Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was used to evaluate the efficacy, and Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 was used to evaluate immune-related adverse. Kaplan-Meier and Log-rank test was performed. Cox regression was used in prognostic analysis. RESULTS: Combined therapy acquired significantly higher overall response rate (ORR) compared with chemotherapy alone in elderly group (P<0.05), and also in younger group, despite the difference was not significant (P>0.05). The median progression-free survival (mPFS) and median overall survival (mOS) in elderly group were similar with younger group (P>0.05). Both combined group and immunology alone demonstrated prolonged mPFS in first-line compared with chemotherapy in elderly group. And combined group demonstrated significantly prolonged mPFS compared with chemotherapy in younger group (P<0.01). There was no difference of mOS between different regimes in two groups. Elderly LUSC patients had higher PD-L1 positive rate (≥1%) and similar TMB compared with younger group. There was no relationship between mPFS and mOS with the expression of PD-L1 and TMB. Immunology combined with chemotherapy demonstrated better mPFS compared to chemotherapy in first-line therapy with TMB-High (P<0.05), and inferior mPFS with TMB-Low despite the difference was not significant (P>0.05). Cox regression model demonstrated that clinical stage was an independent predictor and prognostic factor. The incidence of immune-related adverse was 58.0% (51/88) and grade 3 or above 25.0% (22/88). The most common grade 3 adverse events were rash, immune-associated pneumonia, and fatigue. CONCLUSIONS Immunology combined with chemotherapy increased ORR, mPFS and mOS of Chinese patients with LUSC in first-line therapy compared with chemotherapy. There was no difference of efficacy and adverse effects rate between elderly group and younger group. The adverse effects of immunology in elderly patients with LUSC were controllable.
Aged ; B7-H1 Antigen/analysis* ; Biomarkers, Tumor ; Carcinoma, Non-Small-Cell Lung/pathology* ; Carcinoma, Squamous Cell/drug therapy* ; China ; Humans ; Lung/pathology* ; Lung Neoplasms/pathology*

Objective:To investigate the efficacy and adverse reactions of immunotherapy in elderly patients(≥65 years old)with lung squamous cell carcinoma(LUSC)in Chinese population of real world.Methods:A total of 113 elderly LUSC patients(age ≥65 years old)underwent pathological diagnosis were involved from January 2018 to January 2022.To compare the efficacy of mono-immunotherapy or combined with chemotherapy to chemotherapy in first-line and second-line treatment.44 patients received surgical or minimally invasive treatment, and 69 patients received first-line medical treatment, including 27 patients in chemotherapy group, 24 patients in combined chemotherapy group, and 11 patients in single drug immunization group.7 cases in targeted therapy group.Twenty-eight patients received second-line medical treatment, including 8 patients in chemotherapy group, 11 patients in combined immunochemotherapy(combined group), 4 patients in single drug immunotherapy group, and 5 patients in targeted therapy group.The therapeutic effects and adverse reactions were compared between the first-line and second-line treatments.The expression of programmed death-ligand 1(PD-L1)and tumor mutational burden(TMB)were evaluated.Response evaluation criteria in solid tumors(RECIST)version 1.1 was used to evaluate the efficacy, and common terminology criteria for adverse events(CTCAE)version 4.03 was used to evaluate immune-related adverse.Kaplan-meier and log-rank test was performed.Cox regression was used in prognostic analysis.Results:The total effective rate in the first-line combination group was 73.7%(14/19), higher than that in the chemotherapy group(24.0%, 6/25), and the difference was statistically significant( χ2=10.748, P<0.01). Median progression-free survival(mPFS)was longer in the first-line combination group, the immunization group, and the chemotherapy group, and the median overall survival(mOS)was longer in the combination group, but the differences were not statistically significant(all P<0.05); mOS in the second-line combined group were longer than those in the chemotherapy group, both P<0.01). Elderly patients with lung squamous cell carcinoma had high PD-L1 positive rate(≥1%)and high TMB expression rate(≥9 mut/Mb), 81.6%(31/38)and 57.4%(31/54), respectively.mPFS in the PD-L1 positive group(≥1%)was better than that in the PD-L1 negative group(5.10 months vs.0.93 months, P<0.05). Among PD-L1 positive patients, mPFS in the second-line combination group was better than that in the chemotherapy group(7.33 months vs.2.77 months, P<0.05). mPFS and mOS time were not related to TMB expression.The overall incidence of immune-related adverse reactions was 62.0%(31/50), and 26.0%(13/50)with grade 3 or above.The most common grade 3 adverse events were rash, immune-associated pneumonia, and fatigue. Conclusions:Immunology combined with chemotherapy increased objective response rate, mPFS and mOS of elderly patients with LUSC group in first-line therapy compared with chemotherapy.In second-line treatment, the mOS was significantly prolonged in both combination therapy and mono-immunotherapy, and the combination therapy exhibited no benefit in OS compared with monotherapy.The adverse effects of immunology in elderly patients with LUSC were controllable.

Objective:Immunologic characteristics of differed between younger and older patients.This study aimed to screen potentially key genes related to tumor-infiltrated immune cells(TIICs)in senile patients with lung adenocarcinoma(LUAD).Methods:In this retrospective study, the gene expression data for the training set were extracted from the Cancer Genome Atlas(TCGA)database, and the GSE72094 data set from Gene Expression Database was selected as the validation set.The 91 LUAD patients aged ≥75 years and 14 matched normal samples were screened for analysis.The components of tumor infiltrated immune cells(TIICs)were estimated by the deconvolution algorithm.Then a weighted gene co-expression network analysis was conducted in the training set so as to identify key genes correlating to TIICs.The GSE72094 dataset was used for validation.Results:In elderly patients with LUAD, the high expressions of IKZF1 and PRKCB were related to autoimmune diseases and T cell receptor signaling pathway.And their gene encoding proteins could interact with various immunomodulatory factors, such as IL2RB, LCK, and CD5.In the high expression group of IKZF1 and PRKCB, the expression levels of immunological checkpoint genes such as PD-L1, PD-1 and CTLA-4 were significantly higher than those of the low expression group(all P<0.01). The results of the validation set showed that CD8 + T cells were significantly correlated with the expression of IKZF1( r=0.75, P<0.01)and PRKCB( r=0.65, P<0.01). Conclusions:The expressions of IKZF1 and PRKCB in the tumor tissues are related to tumor infiltrating CD8 T cells and expression of immune checkpoint genes in elderly patients with LUAD.

OBJECTIVE： To investigate the status of sulfur fumigation of TCM and its decoction pieces， and to put forward the suggestions on limit standard of sulfur dioxide residue. METHODS： The information of 374 varieties of TCM and sulfur dioxide residue were collected from the provincial and municipal drug inspection institutions of 27 provinces，municipalities and autonomous regions in China during 2013-2017， and then summarized and analyzed. The average value，median value，maximum value，qualification rate and detection rate of sulfur dioxide residue of 121 varieties with the sample number ≥10 batches were classified and statistically analyzed. RESULTS： This investigation involved 374 varieties of TCM and its decoction pieces， and a total of 13 776 batches of samples. The average content of sulfur dioxide was 242 mg/kg，the median value was 27 mg/kg，and the maximum value was 8 782 mg/kg. The overall qualified rate was 79.7％. According to the results of classified statistics， among the 10 varieties whose limit shall not exceed 400 mg/kg，5 varieties，including Codonopsis pilosula， Radix Trichosanthis， Asparagus cochinchinensis， Pueraria lobata， Achyranthes bidentata， were seriously affected by sulfur fumigation，and the qualified rate was less than 80％. Among the varieties with the sample number≥30 batches， there was no or very little abuse of sulfur fumigation in 16 varieties， such as Carthamus tinctorius； 19 varieties， such as Eupolyphaga Steleophaga， had excessive sulfur fumigation， but it was not serious； 25 varieties，such as Lonicera japonica，had severe excessive sulfur fumigation. Among the varieties with the sample number of 10-29 batches，33 varieties including Ziziphus jujube seed had no or very little abuse of sulfur fumigation； 8 varieties including Cuscuta chinensis had excessive sulfur fumigation but were not serious； 10 varieties including Pericarpium Trichosanthis had serious excessive sulfur fumigation. CONCLUSIONS： For the varieties with no or very little excessive sulfur fumigation，it is recommended that batch testing should not be carried out and a single list should be made； for the varieties with sulfur fumigation or severe sulfur fumigation， it is suggested to increase the sulfur dioxide residue limit under all varieties in the 2020 edition of Chinese Pharmacopoeia， and set the limit for the varieties with severe sulfur fumigation to be no more than 400 mg/kg，while the limit for the 2025 edition of Chinese Pharmacopoeia can be reduced to no more than 150 mg/kg. Other varieties should retain the provisions of “sulfur dioxide residue of sulfur dioxide medicinal materials and decoction pieces （except for minerals） shall not exceed 150 mg/kg” in the general rules 0212 “for the identification of medicinal materials and decoction pieces” in the 2015 edition of Chinese Pharmacopoeia （part Ⅳ）.

"Bangjian" were traditional Tibetan medicine-flowers from Gentianaceae, which were widely used and had a long medicinal history for the function of detoxifying, curing heat symptoms and treating the laryngitis. The Tibetan compound preparation endowed SFDA approval number always used Bangjian aas the main raw materials for relieving cough, asthma and treating respiratory diseases such as acute and chronic bronchitis. Its commodity medicinal materials were also sold in Qinghai, Sichuan, Tibet and other local medicinal materials market and local specialty marke. However, when recorded by literatures of Tibetan medicine, Bangjian were often classified into white, blue and black or white, blue and variegated according to color of flowers, leading to disordered varieties. In this paper, different Bangjian including their original plants and the main application varieties were studied and authenticated by textual research, wild specimen collection, investigation and collection of samples from Tibetan hospitals，Tibetan pharmaceutical factories and medical material markets. Results showed that Bangjian-including blue, black and variegated flowers were originated from 14 species and 3 varietas according to literatures, and the main application varieties mainly come from Ser. Ornatae of Sect. Monopodiae, such as Gentiana veitchiorum for the most, G. sino-ornata as well as G. lawrencei var. farreri. Suggestion about establishing the quality standard of Bangjian was gived, which provided reference in reasonable use and scientific research for Bangjian, and also had practical value for its clinical use and development.

Tibetan ancient literature is an important foundation for the development of Tibetan medicine and clinical research. The essential features and advantages of inheritance and development of Tibetan medicine play an ines-timable role. Jing-Zhu Materia Medica is by far the most important Tibetan medicine monograph. This book is rich in content, national characteristics, featured prominent plateau, which is practical in the clinical application. This ar-ticle analyzed the literature value and academic characteristics of Jing-Zhu Materia Medica from the drug classifi-cation, medicinal processing method, and comparison between Tibetan medicine and Chinese medicine. It promoted the analysis of ancient Tibetan medicine literatures to provide references for the scientific research, medical practice and application development of Tibetan medicine.

OBJECTIVETo provide a reference for the standardization of Tibetan medicine.

METHODInvestigating the hospital preparations , Tibetan formulated products, and the literature recorded preparations in the Tibetan, Qinghai, Gansu, Sichuan and Yunnan Provinces. Moreover, the varieties, original bases and standard conditions of these preparations were analyzed. According to Chinese Pharmacopoeia, Tibetan medicine part of ministerial standard, Tibetan medicine standards and related monographs and literatures of Tibetan medicine.

RESULTAbout 502 various of herbs were used in 711 hospital preparations from 40 medical institutions, Tibetan formulated products from Tibetan pharmaceutical factories, and 439 literature recorded preparations. About 154 herbs were used in more than 10 preparations, while most of them were Tibetan endemic species. About 416 medicinal varieties have the original documented basis, including 287 botanicals, 78 animal medicines, 51 mineral medicines, involving a total of 94 families, 261 genus and 643 species of botanical origin (including species of the next grade), 35 families, 52 genera and 61 species of the animal origin (including species of the next grade). About 122 varieties of herbs were cross-used in the traditional Chinese medicine and Tibetan medicine, about 80% of Tibetan medicinal varieties are produced in the Tibetan Areas of Tibet Plateau. About 293 medicinal varieties were contained in the above standards. Most of the herb's standards only contains character, indentification, and examination, except for 8 varieties which were recorded in the Chinese Pharmacopoeia (2010) as Tibetan medicine.

CONCLUSIONThis study of quality standard of Tibetan medicine should have an emphasis on the general varieties, especially the study on the arrangement research and the efficacious material basis of the varieties and the original, as well as term standardization of the National Medicine.

ObjectiveTo explore the efficacy and safety of percutaneous antegrade stenting in the treatment of ureteral obstruction after renal transplantation.MethodsWe retrospectively reviewed 11patients with renal graft ureteral obstruction (2 cases of acute obstruction and 9 cases of chronic obstruction) from March 2009 to March 2011.The etiology of the obstruction was renal graft-ureter-bladder anastomotic stricture in 5 cases,stone obstruction in 2 cases,and undetermined in 4 cases.Renal graft and collecting system were examined by ultrasonography preoperatively to select suitable puncture position,and then ureteropyelography was performed under X-ray guidance.When the obstruction location was clear,the urology guidewire was implanted to the bladder by needle,and then guidewire was released by cystoscopy.Ureteral stent was implanted along the guidewire,and upper ureteral stents was observed under X-ray. After removal of guidewire,the stent location was confirmed once again.The renal pelvis fistula drainage lasted for 1-2 weeks,and ureteral stent to 6 months to one year.Ultrasound and renal function were tested after 1week,1month,3 months and 6 months,and then every six months.ResultsOperation was done successfully in 10 patients,and failed in one case due to a long segment of ureteral stenosis.The operating time of ureteral stent implantation was 54±27 min.Serum creatinine of patients was reduced from preoperative 326±147 to postoperative 89±49 μmol/L.During a follow-up period of 6 to 27 months,no complications occurred.ConclusionPercutaneous antegrade stenting in the treatment of ureteral obstruction after renal transplantation is safe and effective.